An ecofriendly, inexpensive, and efficient route for synthesizing 3,3′-bis(indolyl)methanes (BIMs) and their derivatives was carried out by an electrophilic substitution reaction of indole with structurally divergent aldehydes and ketones using taurine and water as a green catalyst and solvent, respectively, under sonication conditions. Using water as the only solvent, the catalytic process demonstrated outstanding activity, productivity, and broad functional group tolerance, affording the required BIM natural products and derivatives in excellent yields (59–90%). Furthermore, in silico based structure activity analysis of the synthesized BIM derivatives divulges their potential ability to bind antineoplastic drug target and spindle motor protein kinesin Eg5. The precise binding mode of BIM derivatives with the ATPase motor domain of Eg5 is structurally reminiscent with previously reported allosteric inhibitor Arry520, which is under phase III clinical trials. Nevertheless, detailed analysis of the binding poses indicates that BIM derivatives bind the allosteric pocket of the Eg5 motor domain more robustly than Arry520; moreover, unlike Arry520, BIM binding is found to be resistant to drug-resistant mutations of Eg5. Accordingly, a structure-guided mechanism of Eg5 inhibition by synthesized BIM derivatives is proposed.

The class of Double Diels‐Alder (DDA) reactions leading the targets concisely where numerous synthetic pursuits have been rewarded with conceptually novel and streamlined methods. After the tremendous development and discoveries in various Diels‐Alder reactions including its key role applications in many natural products syntheses, the DDA reaction is considered as a growing branch of Diels‐Alder reaction where two consecutive [4+2] cycloadditions trigger the streamlined construction of polycyclic and macrocyclic architectures. In light of the ever‐increasing importance of DDA reactions in chemical sciences, we review the comprehensive studies and recent advances in DDA reactions in organic synthesis. This review summarizes key achievements of DDA for the preparation of macrocyclic, bicyclic, heterocyclic, and polycyclic structures documented since its revelation in 1980 to 2020. Emphasis is put on the synthesis of various structural classes based on the selectivity of the DDA reaction.

This review features a broad interest in compiling a range of cascade transformations under various classifications based on nature and reactivity of the main ingredient to solve diverse challenges in organic synthesis to create fascinating molecules.

Many natural products and biologically important complex organic scaffolds have convoluted structures around their core skeleton. Interestingly, with just changing the outskirts, the core reflects new and unique degrees of various physical and chemical properties. A very common but intriguing core is a five-membered ring horning heaps of organic molecules crafts. The power of [3+2] cycloaddition reactions to generate five-membered ring systems allocate chemists to envision synthetic procedures of wonder molecules and if it is facilitating a cascade sequence, then the end product will imbibe significant level of complexity having applications in medicinal and pharmaceutical fields. This Account highlights the broad interest in assembling recent advances in cascade reactions involving [3+2] cycloaddition as the power tool in order to conceive breakthrough organic architectures reported in the last ten years. We foresee that our comprehensive collection of astonishing [3+2] cycloaddition enabled cascades will provide valuable insights to polycyclic molecular construction and perseverant approach towards nonconventional synthetic procedures to the organic community.1 Introduction2 Synthesis of Oxindoles Skeleton3 Synthesis of Oxazoles Skeleton4 Synthesis of Oxadiazoles Skeleton5 Synthesis of Nitrogen-Containing Heterocycles6 Synthesis via Formal [3+2] Cycloaddition7 Synthesis of Miscellaneous Scaffolds8 Conclusion

The Diels‐Alder (DA) reaction is one of the fascinating synthetic strategies known for its pericyclic action and concerted mechanism that leads to various targets. Numerous synthetic pursuits have been rewarded with conceptually distinct and efficient ways. To date, extensive and spectacular accomplishments have been made in the field of Diels‐Alder chemistry to overcome the complexities of organic synthesis that inspired organic chemists to focus on expanding and establishing the postulates. In principle, DA reactions are governed by their straightforward reactivity pattern with a high degree of certainty, primarily attributed to the HOMO‐LUMO separation of reacting partners. Furthermore, general forecasts rely on account of background studies, conveniently hypothesizing the stereochemical outcomes and reaction dynamic pathways. DA has recently emerged as a technique for establishing a variety of products from the same reacting species under varying reaction conditions rather than a general reactivity profile. Such exceptional results are of significant interest in organic synthesis to pursue the challenges of unanticipated product establishment. Herein, we summarize the impressive finding of the remarkable switch in the regioselectivity and diastereoselectivity of DA reactions under a diverse set of reaction protocols in light of Diels‐Alder's unending importance in chemical science. This review aims to establish a beneficial account of Diels‐Alder towards the astonishing switches extended to study varying synthetic versions in organic synthesis protocols attributed to natural and biologically active scaffolds. This review also provides insight into distinct reaction dynamics in DA reactions that are subjected to access molecular frameworks ranging from simple to complicated ones to foster high levels of innovation in chemical sciences.